The objective of this proposal is to use laboratory techniques, primarily immunologic, to explore diagnostic and therapeutic approaches to human allergic disorders with the aim of improving these techniques and thereby the clinical care of allergic disorders. We will determine patient sensitivity by histamine release, skin testing and the IgE antibody measurements and protection by IgE antibody measurements. Studies will include the measurement of IgE and IgG antibodies against an array of isolated allergens and RAST inhibition; we will also seek to demonstrate the degree and frequency of IgE heterogeneity, both with respect to Fc and Fab portions of the molecule. Two types of allergy will be studied: parenterally induced, typified by Hymenoptera sensitivity, and inhalant allergy, typified by asthma and rhinitis to pollen or dander antigens. With respct to insect allergy, we will try to determine which patients require therapy in the context of the cost and effectiveness. We will study the crossreactivity among the vespid venoms, with the hypothesis that most patients are sensitive only to yellow jacket and, therefore, require therapy only with this venom. We will use modified venom antigens in an attempt to decrease the incidence of local and systemic reactions during immunotherapy. The regimens of immunotherapy will be further explored and a possible endpoint searched for. Finally, an epidemiologic study of the incidence of clinical and immunologic sensitivity to insect venoms will be executed. With respect to inhalant allergy, we will begin studies using antigens which, in animals, are "tolerizing" with respect to IgE production. This will involve, primarily, ragweed allergens modified by the introducton of polyethylene glycol groups or by DGL. Using standard antigen preparations, we will evaluate the immunotherapy of asthma to cat dander, assessing response by bronchoprovocation and controlled environmental exposure. In each of these studies we will follow the immunotherapeutic effects by antibody measurements and controlled clinical trials to determine efficacy. We will attempt to establish a relationship between the immunologic measurements and the clinical result.